特发性正常压力脑积水中的α-突触核蛋白病理：合并突触核蛋白病的证据及临床意义

文献信息

中文摘要

特发性正常压力脑积水（iNPH）是一种潜在可逆的神经系统疾病，以步态障碍、认知功能下降和排尿功能障碍为特征。尽管诊断标准和神经影像技术不断改进，但由于其与神经退行性疾病，尤其是阿尔茨海默病（AD）和突触核蛋白病存在临床重叠，准确诊断仍具挑战性。因此，能够改善鉴别诊断、分流手术患者筛选和预后评估的生物标志物具有相当大的临床意义，正如AD生物标志物那样。本综述总结了当前关于α-突触核蛋白作为iNPH潜在附加标志物作用的证据，重点关注其与合并神经退行性病理、临床表现及治疗结局的关联。现有研究表明，α-突触核蛋白病理可能在相当比例的患者中与iNPH共存，报告的阳性率约为14%至33%，具体取决于所采用的检测方法。合并α-突触核蛋白病理的患者可能表现出非单纯iNPH的临床特征，包括上肢强直、嗅觉功能障碍、幻觉、自主神经功能障碍、睡眠障碍以及波动性认知损害。然而，当前证据并不支持α-突触核蛋白阳性可作为脑脊液（CSF）引流或分流手术反应不良的独立预测因素。相反，α-突触核蛋白的存在可能为混合性神经退行性病理提供额外信息，并有助于个体化临床管理。未来研究应聚焦于标准化检测技术、更大型的多中心队列、纵向随访，以及将α-突触核蛋白评估与已确立的AD生物标志物、神经影像学发现和临床评估相结合。总体而言，α-突触核蛋白是iNPH中一种有前景的补充标志物，在临床评估和理解疾病异质性方面具有潜在价值。

英文摘要

Idiopathic normal pressure hydrocephalus (iNPH) is a potentially reversible neurological disorder characterized by gait impairment, cognitive decline, and urinary dysfunction. Despite improvements in diagnostic criteria and neuroimaging techniques, accurate diagnosis remains challenging due to clinical overlap with neurodegenerative diseases, particularly Alzheimer's disease (AD) and synucleinopathies. Biomarkers capable of improving differential diagnosis, patient selection for shunt surgery, and prognostic assessment are therefore of considerable clinical interest, as has been in AD biomarkers. This review summarizes current evidence regarding the role of α-synuclein as a potential additional marker in iNPH, focusing on its association with concomitant neurodegenerative pathology, clinical manifestations, and treatment outcomes. Available studies indicate that α-synuclein pathology may coexist with iNPH in a substantial proportion of patients, with reported positivity rates ranging from approximately 14% to 33%, depending on the detection method used. Patients with concomitant α-synuclein pathology may exhibit clinical features atypical for pure iNPH, including upper limb rigidity, olfactory dysfunction, hallucinations, autonomic dysfunction, sleep disturbances, and fluctuating cognitive impairment. However, current evidence does not support α-synuclein positivity as an independent predictor of poor response to cerebrospinal fluid (CSF) drainage or shunt surgery. On the contrary, α-synuclein presence may provide additional information regarding mixed neurodegenerative pathology and contribute to personalized clinical management. Future studies should focus on standardized detection techniques, larger multicenter cohorts, longitudinal follow-up, and integration of α-synuclein assessment with established AD biomarkers, neuroimaging findings, and clinical evaluation. Overall, α-synuclein represents a promising complementary marker in iNPH, with potential value in being taken into consideration during clinical evaluation and understanding disease heterogeneity.